Neuroprotective effect of safflower yellow in mice with cerebral ischemia reperfusion injury

Safflower yellow (SY), a bioactive compound from Carthamus tinctorius L., possesses potent antioxidant and anti-inflammatory properties and may exert protective effects on vulnerable brain regions during acute global ischemia. Therefore, this study aimed to evaluate the neuroprotective effects of SY against cerebral ischemia-reperfusion (IR) injury in mice, focusing on oxidative status, hippocampal neuronal survival, and white matter integrity. Forty male (Institute of Cancer Research) ICR mice were assigned to Sham-veh, IR-veh, IR-SY50, and IR-SY100 groups. Pretreatment with SY or vehicle was performed for 2 weeks before IR induction by 30-min bilateral common carotid artery occlusion and 24-h reperfusion. Brain infarct volume, oxidative status, and histological changes in the hippocampus and corpus callosum (CC) were evaluated. Significantly increased lipid peroxidation and cerebral infarction, depletion of catalase (CAT) activity, selective neuronal death in the Cornus Ammonis 1 (CA1) region, and loss of CC white matter integrity were clearly depicted after IR induction. Pretreatment with SY doses of 50 and 100 mg/kg significantly attenuated brain infarct volume, together with upregulated superoxide dismutase and catalase activities. Histological analysis revealed a dose-dependent therapeutic threshold. Only SY at 100 mg/kg significantly prevented neuronal death in the CA1 region and preserved CC white matter integrity. Pretreatment with SY exhibits neuroprotective effects against IR primarily by enhancing endogenous antioxidant defenses. Crucially, while biochemical improvements are achievable at lower doses, a higher therapeutic dose is required to preserve neuronal and white matter structural integrity in selectively vulnerable brain regions.